The modulation of insulin-stimulated glucose transport activity in rat adipose cells by ligands for receptors (R) that mediate stimulation (Rs; lipolytic) or inhibition (Ri; antilipolytic) of adenylate cyclase has been examined. The results suggest that 1) Ri- and Rs-mediated effects on glucose transport are independent of changes in cAMP, 2) these cAMP-independent effects are mediated by GTP-binding proteins, Ni and Ns, and 3) Ri and Rs ligands modulate the intrinsic activity of the glucose transporter in the plasma membrane. The mechanism of modulation of insulin-stimulated glucose transport activity in isolated rat adipose cells by lipolytic and antilipolytic agents has been further examined by measuring glucose transport activity in plasma membranes. The data indicate that modifications of glucose transport activity produced by lipolytic and antilipolytic agents in intact adipose cells can be fully retained in plasma membranes isolated under appropriate conditions, further supporting the concept that the effects of these agents occur through a modification of glucose transporter intrinsic activity. The effects of beta-adrenergic stimulation and different analogues of cAMP on insulin-stimulated IGF-II binding have also been studied. The results indicate that beta-adrenergic stimulation and high levels of cAMP markedly impair both sensitivity and responsiveness to insulin suggesting an antagonistic effect on insulin's signalling mechanism. Furthermore, adenosine appears to exert a potent modulating effect through Ni, while activation of phosphodiesterase by insulin appears to play a crucial role for the expression of insulin action under conditions of elevated cAMP levels. The counterregulatory action of catecholamines on insulin-stimulated glucose transport and its relation to glucose transporter phosphorylation have been studied in isolated rat adipose cells. The results suggest that the phosphorylation state of the glucose transporter does not appear to be involved in either signalling glucose transporter translocation or triggering changes in glucose transporter intrinsic activity.